Ultrasound system for cerebral blood flow imaging and microbubble-enhanced blood clot lysis

ABSTRACT

An ultrasonic diagnostic imaging system is described which utilizes one or more transducer arrays affixed to the head of a patient to diagnose and treat stroke victims. The transducer headset produces a two or three dimensional image of the vasculature inside the cranium, preferably assisted by a microbubble contrast agent. A vascular flow map is produced by the system which may be diagnosed for signs of a blood clot. If a blood clot is detected, a therapeutic beam is transmitted while the contrast agent is present to break up the blood clot by the disruption of microbubbles. The headset may also be used in a monitoring application to detect the recurrence of blood clots in a stroke victim.

This application claims the benefit of International ApplicationPCT/IB07/53073, filed on Aug. 3, 2007, which in turn claims the benefitof U.S. provisional patent application Ser. No. 60/822,106 filed on Aug.11, 2006.

This invention relates to medical diagnostic ultrasound systems and, inparticular, to ultrasound systems which perform imaging and therapy forstroke victims.

Ischemic stroke is one of the most debilitating disorders known tomedicine. The blockage of the flow of blood to the brain can rapidlyresult in paralysis or death. Attempts to achieve recanalization throughthrombolytic drug therapy such as treatment with tissue plasminogenactivator (tPA) has been reported to cause symptomatic intracerebralhemorrhage in a number of cases. Advances in the diagnosis and treatmentof this crippling affliction are the subject of continuing medicalresearch.

Transcranial Doppler ultrasound has been developed for use in monitoringand diagnosing stroke. A headset device manufactured by SpencerTechnologies of Seattle, Wash., USA holds two transducers against theside of the skull, one on each temporal bone just in front of the ear.The transducers transmit ultrasonic waves through the temporal bone andthe returning echo signals are Doppler processed and the phase shiftinformation reproduced at audible frequencies. The audible Doppleridentifies the presence or absence of blood flow inside the cranium asthe clinician listens for characteristic sounds of blood flow velocitiesof specific arteries. The technique can also be augmented with aspectral Doppler display of the phase shift information, providinginformation on flow velocities inside the cranium. However, since thereis no information concerning the anatomy inside the skull, the clinicianmust attempt to make a diagnosis on the basis of this limitedinformation. This diagnostic approach is also very technique-dependentand is performed by highly trained individuals.

Recently Dr. Andrei Alexandrov of the University of Texas Medical Schoolat Houston, Tex. found that the application of ultrasound during tPAtreatment improved the efficacy of tPA for stroke treatment. Dr.Alexandrov observed that the micro-vibrations of the ultrasonic waveswork on the surface of the blood clot to open up a larger surface thatthe tPA can then bind to and penetrate. Dr. Alexandrov is now leading aresearch team which is investigating the added efficacy of addingultrasonic contrast agent microbubbles to the tPA or using microbubblesand ultrasound alone to dissolve blood clots. It is also contemplatedthat microbubbles may be targeted to components in the blood clot suchas fibrin and stick to the clot, increasing the concentration andeffectiveness of the treatment. Targeted nanoparticles are anotherpossibility for this procedure. It is thus believed by many thatultrasound together with thrombolytic drugs, microbubbles, or both canlead to significant improvement in stroke treatment.

In accordance with the principles of the present invention, a diagnosticultrasound system and method are described which enable a clinician totranscranially visualize a region of the cerebral vasculature whereblood clots may be present. Either two dimensional or three dimensionalimaging may be employed. The imaging of the vasculature is preferablyenhanced by the administration of microbubbles. If the flow conditionsof the vasculature indicate the presence of a partial or completeocclusion, a focused or pencil beam is directed to the location of theblockage to break up the clot by the vibrations and/or rupturing of themicrobubbles. In some instances the ruptured microbubbles may alsorelease an encapsulated thrombolytic drug. In accordance with a furtheraspect of the present invention, the cranial vasculature may bemonitored by ultrasonic imaging for changes which are indicative of therecurrence of an occlusion, and medical aid alerted to the condition.

In the drawings:

FIG. 1 illustrates in block diagram form an ultrasonic diagnosticimaging system constructed in accordance with the principles of thepresent invention.

FIGS. 2a and 2b illustrate a safety helmet liner suitable for use in atranscranial imaging transducer headset.

FIG. 3 illustrates a procedure for ultrasonically imaging the cranialvasculature and dissolving blood clots in accordance with the principlesof the present invention.

FIG. 4 illustrates three dimensional transcranial imaging in accordancewith the present invention.

FIG. 5 illustrates two dimensional transcranial imaging in accordancewith the present invention.

FIGS. 6a-6d illustrate treatment of a cranial occlusion in accordancewith the principles of the present invention.

FIG. 7 illustrates a procedure for ultrasonically monitoring for cranialocclusions in accordance with the present invention.

Referring first to FIG. 1, an ultrasound system constructed inaccordance with the principles of the present invention is shown inblock diagram form. Two transducer arrays 10 a and 10 b are provided fortransmitting ultrasonic waves and receiving echo information. In thisexample the arrays shown are two dimensional arrays of transducerelements capable of providing 3D image information although animplementation of the present invention may also use two dimensionalarrays of transducer element which produce 2D (planar) images. Thetransducer arrays are coupled to microbeamformers 12 a and 12 b whichcontrol transmission and reception of signals by the array elements.Microbeamformers are also capable of at least partial beamforming of thesignals received by groups or “patches” of transducer elements asdescribed in U.S. Pat. No. 5,997,479 (Savord et al.), U.S. Pat. No.6,013,032 (Savord), and U.S. Pat. No. 6,623,432 (Powers et al.) Signalsare routed to and from the microbeamformers by a multiplexer 14 bytime-interleaving signals. The multiplexer is coupled to atransmit/receive (T/R) switch 16 which switches between transmission andreception and protects the main beamformer 20 from high energy transmitsignals. The transmission of ultrasonic beams from the transducer arrays10 a and 10 b under control of the microbeamformers 12 a and 12 b isdirected by the transmit controller 18 coupled to the T/R switch, whichreceived input from the user's operation of the user interface orcontrol panel 38.

The partially beamformed signals produced by the microbeamformers 12 a,12 b are coupled to a main beamformer 20 where partially beamformedsignals from the individual patches of elements are combined into afully beamformed signal. For example, the main beamformer 20 may have128 channels, each of which receives a partially beamformed signal froma patch of 12 transducer elements. In this way the signals received byover 1500 transducer elements of a two dimensional array can contributeefficiently to a single beamformed signal.

The beamformed signals are coupled to a fundamental/harmonic signalseparator 22. The separator 22 acts to separate linear and nonlinearsignals so as to enable the identification of the strongly nonlinearecho signals returned from microbubbles. The separator 22 may operate ina variety of ways such as by bandpass filtering the received signals infundamental frequency and harmonic frequency bands, or by a processknown as pulse inversion harmonic separation. A suitablefundamental/harmonic signal separator is shown and described ininternational patent publication WO 2005/074805 (Bruce et al.) Theseparated signals are coupled to a signal processor 24 where they mayundergo additional enhancement such as speckle removal, signalcompounding, and noise elimination.

The processed signals are coupled to a B mode processor 26 and a Dopplerprocessor 28. The B mode processor 26 employs amplitude detection forthe imaging of structures in the body such as muscle, tissue, and bloodcells. B mode images of structure of the body may be formed in eitherthe harmonic mode or the fundamental mode. Tissues in the body andmicrobubbles both return both types of signals and the harmonic returnsof microbubbles enable microbubbles to be clearly segmented in an imagein most applications. The Doppler processor processes temporallydistinct signals from tissue and blood flow for the detection of motionof substances in the image field including microbubbles. The structuraland motion signals produced by these processors are coupled to a scanconverter 32 and a volume renderer 34, which produce image data oftissue structure, flow, or a combined image of both characteristics. Thescan converter will convert echo signals with polar coordinates intoimage signals of the desired image format such as a sector image inCartesian coordinates. The volume renderer 34 will convert a 3D data setinto a projected 3D image as viewed from a given reference point asdescribed in U.S. Pat. No. 6,530,885 (Entrekin et al.) As describedtherein, when the reference point of the rendering is changed the 3Dimage can appear to rotate in what is known as kinetic parallax. Thisimage manipulation is controlled by the user as indicated by the DisplayControl line between the user interface 38 and the Volume renderer 34.Also described is the representation of a 3D volume by planar images ofdifferent image planes, a technique known as multiplanar reformatting.The volume renderer 34 can operate on image data in either rectilinearor polar coordinates as described in U.S. Pat. No. 6,723,050 (Dow etal.) The 2D or 3D images are coupled from the scan converter and volumerenderer to an image processor 30 for further enhancement, buffering andtemporary storage for display on an image display 40.

A graphics processor 36 is also coupled to the image processor 30 whichgenerates graphic overlays for displaying with the ultrasound images.These graphic overlays can contain standard identifying information suchas patient name, date and time of the image, imaging parameters, and thelike, and can also produce a graphic overlay of a beam vector steered bythe user as described below. For this purpose the graphics processorreceived input from the user interface 38. The user interface is alsocoupled to the transmit controller 18 to control the generation ofultrasound signals from the transducer arrays 10 a and 10 b and hencethe images produced by and therapy applied by the transducer arrays. Thetransmit parameters controlled in response to user adjustment includethe MI (Mechanical Index) which controls the peak intensity of thetransmitted waves, which is related to cavitational effects of theultrasound, steering of the transmitted beams for image positioningand/or positioning (steering) of a therapy beam as discussed below.

The transducer arrays 10 a and 10 b transmit ultrasonic waves into thecranium of a patient from opposite sides of the head, although otherlocations may also or alternately be employed such as the front of thehead or the sub-occipital acoustic window at the back of the skull. Thesides of the head of most patients advantageously provide suitableacoustic windows for transcranial ultrasound at the temporal bonesaround and above the ears on either side of the head. In order totransmit and receive echoes through these acoustic windows thetransducer arrays must be in good acoustic contact at these locationswhich may be done by holding the transducer arrays against the head witha headset. For instance, FIG. 2a shows a conventional safety helmet 200which is adjustably held on the wearer's head by a helmet liner 202shown in the view of FIG. 2b . The helmet liner wraps securely about thecircumference of the wearer's head. Transducer arrays positioned insidethe helmet liner on either side as indicated by the locations of circles204,206 will be held securely against the skin of the temporal bones ofthe wearer, enabling the helmet liner 202 to function as a transcranialultrasound headset. The helmet liner headset is adjustably secured inplace by an adjustment knob 208. An occipital transducer would bepositioned at or below the location of adjustment knob 208. The headsethas one or more straps 210 which pass over the top of the head foradjustment of the vertical position of the headset. These straps andother adjustable members of the headset can be elastic or adjustablethrough other means such as buckles or Velcro®. When properly adjustedthe headset will hold the acoustic transducer arrays securely in goodacoustic contact on the temples of the patient. Acoustic coupling may beaided by applying an acoustic coupling gel between the transducer andthe skin.

A procedure in accordance with the present invention which uses theultrasound system and transcranial ultrasound headset just described isillustrated by the flowchart of FIG. 3. In step 60 the headset is put onthe patient with the transducer arrays in acoustic contact with the skinof the patient. The system is activated to image inside the cranium andin step 62 the headset is adjusted until flow inside the cranium can beseen in the ultrasound image of one or (when displayed in duplex) bothof the transducer arrays. The colorflow imaging mode of the system ispreferably used at this time to produce a two or three dimensional imageof the bloodflow inside the cranium. If the cranial flow can be seen incolorflow, the other steps of this procedure can be expected to proceedas desired. When the flow is seen in the ultrasound images the headsetis tightened in step 64 to secure the transducer array in their imagingpositions. FIG. 4 illustrates the situation at this point for 3Dimaging. In this illustration the transducer arrays 10 a,10 b are heldagainst the sides of the skull 100 and are imaging 3D image fields102,104 inside the cranium. The user will see one or both of the 3Dimage fields 102,104 on the display of the ultrasound system in either amultiplanar or volume rendered 3D projection. The user can manipulatethe kinetic parallax control to observe the volume rendered 3D imagefrom different orientations. The user can adjust the relative opacity ofthe tissue and flow components of the 3D image to better visualize thevascular structure inside the brain tissue as described in U.S. Pat. No.5,720,291 (Schwartz) or can turn off the B mode (tissue) portion of thedisplay entirely and just visualize the flow of the vascular structureinside the 3D image field 102,104.

When the cranium is being imaged successfully a microbubble contrastagent is introduced into the patient's bloodstream at step 66. In ashort time the microbubbles in the bloodstream will be pumped throughthe carotid arteries and into the cranial vascular system and appear inthe image. The clinician user is now able to begin a diagnostic searchfor blood clots occluding blood vessels in the brain, looking forbranches of the vasculature which terminate or are only dimly lighted byecho returns from microbubbles due to a partial occlusion. When a dualdisplay from both transducer arrays is present the clinician is alsoable to compare the relative symmetry of the two displayed regions,looking for signs of asymmetry. If the clinician finds no signs ofocclusion in the vasculature presently being viewed by the image fields102,104, the clinician can steer the image field to other regions of theanatomy as indicated by step 68. Steering the image field can be donemechanically by physically adjusting the position of a transducer arrayto aim its image field through different anatomy of the brain.Preferably, the clinician is able to adjust the steering of the beamsfrom the transducer array with a control on the user interface. Byadjusting this control (the Beam Steer control line to the transmitcontroller 18), the clinician is able to electronically steer the imagefield around inside the skull without disturbing the acoustic couplingof the array against the head of the patient.

At each position of the image field 102,104 the clinician can look forobstructions of the blood flow in the real time images on the display,or can capture (freeze) an image or map of the cranial vasculature asindicated in step 70. When the vascular map is acquired and heldstatically, the image can undergo enhanced processing (e.g.,compounding, signal averaging) to improve the resolution or scale of theimage and can be manipulated on the screen and examined carefully atdifferent points and from different views in a precise search for bloodvessel occlusions. In this way the clinician can diagnose for stenosesas indicated at step 72. If the clinician examines a vascular map andfinds no evidence of obstruction in the blood flow paths, the cliniciancan steer the image field to another region of the cranium and examinethe vascular map of another image field. The clinician can use theDoppler data of the vascular map or the spectral Doppler function of theultrasound system to take flow velocity measurements at specific pointsin the cranial vasculature, then use the report generation capabilitiesof the ultrasound system to record the measurements and prepare a reportof his diagnosis.

Examples of vascular maps are shown in FIGS. 6a-6c . FIG. 6a illustratesa vascular network 300 of blood vessels. When only flow imaging isperformed and the flow image is displayed in the absence of anysurrounding B mode tissue structure, as described in U.S. Pat. No.5,474,073 (Schwartz et al.), only the flow of the vasculature is shownwithout any obscuring surrounding structure as FIG. 6a illustrates. Thevascular network 300 may be displayed in two dimensions, threedimensions, and by various Doppler techniques such as colorflow(velocity) Doppler or power (intensity) Doppler. In the absence ofstenoses the flow network will appear continuous and with velocities andintensities proportionate to vessel size. But if a branch 302 of thevascular network is obstructed, the flow will appear different, e.g.,higher velocity and/or intensity, and, if completely obstructed, willdisappear entirely in the Doppler flow map as shown in FIG. 6c . Bydiscerning characteristics such as these, the clinician can diagnose astenosis, then direct a therapeutic beam 110 to the suspected locationof the obstruction of the vessel as shown in FIG. 6 d.

If the clinician discovers a stenosis, therapy can be applied byagitating or breaking microbubbles at the site of the stenosis in aneffort to dissolve the blood clot. The clinician activate the “therapy”mode, and a graphic 110,112 appears in the image field 102,104,depicting the vector path of a therapeutic ultrasound beam. Thetherapeutic ultrasound beam is manipulated by a control on the userinterface 38 until the vector graphic 110,112 is focused at the site ofthe blockage, as indicated by step 74. The therapeutic beam can be atightly focused, convergent beam or a beam with a relatively long focallength known as a pencil beam. The energy produced for the therapeuticbeam can be in excess of the ultrasound levels permitted for diagnosticultrasound, in which case the microbubbles at the site of the blood clotwill be sharply broken. The energy of the resulting microbubble ruptureswill strongly agitate the blood clot, tending to break up the clot anddissolve it in the bloodstream. However in some instances insonificationof the microbubbles at diagnostic energy levels may be sufficient todissolve the clot. Rather than breaking in a single event, themicrobubbles may be vibrated and oscillated, and the energy from suchextended oscillation prior to dissolution of the microbubbles can besufficient to break up the clot, as indicated at step 76.

A particularly effective way to insonify the microbubbles is known as“flash” transmission. In flash transmission, insonification is halted toallow the flow of blood to deliver a substantial volume of microbubblesto the site of the blockage. At the end of this pause, a rapid series ofhigh MI pulses are transmitted to rapidly and energetically rupture themicrobubbles, which releases energy at the site of the blockage. The gasfrom the ruptured microbubbles dissolves in the bloodstream. Anotherpause period commences to allow the buildup of a fresh supply ofmicrobubbles and the process continues. See U.S. Pat. No. 5,560,364(Porter) and U.S. Pat. No. 5,685,310 (Porter). The flash technique wasimproved with the discovery that imaging can be performed at low MIlevels as the microbubbles accumulate, enabling the clinician tovisually monitor the buildup of microbubbles and determine the optimaltime to administer the high MI flash. See U.S. Pat. No. 6,171,246(Averkiou et al.)

In accordance with a further aspect of the present invention, it hasbeen found that a low duty cycle flash will create rapid microbubbledestruction within the energy limits of diagnostic ultrasound. There isthus no need to expose the patient to possibly harmful therapeuticexposure levels. In this technique, the flash pulses are deliveredwithin the MI (instantaneous pressure) limits of diagnostic ultrasound.Another energy limit parameter for ultrasound is the spatial peaktemporal average (SPTA), which is a measure of the average energydelivered over time and is related to temperature rise. It has beendiscovered that a series of high MI pulses (within diagnostic limits)will cause the targeted microbubbles to break up and dissolve in thebloodstream in 100-300 milliseconds. Thus, continued insonification isof no effect, for virtually no microbubbles remain after this period. Inthe inventive technique, the high MI pulse period has a duty cycle of50% or less. For instance, the high MI pulses may be delivered for 200ms, after which high MI pulses are inhibited for the following 800 msec.The duty cycle of the high MI pulse delivery period is thus only 20%.Needless high MI pulses are inhibited and the time averaged energydelivered over the one second interval is within the temporal averagelimits of the SPTA parameter. Furthermore, new microbubbles are allowedto reinfuse the blood clot site as soon as the high MI transmission hasceased. Moreover, longer pulse lengths may be employed during the highMI portion of the duty cycle, which have been found to be very effectivefor microbubble disruption.

The type of stroke suffered by a patient can be either hemorrhagicstroke or ischemic stroke. Hemorrhagic stroke, which may for instance becaused by a ruptured aneurism, results in blood flow outside of bloodvessels and will not be improved by treatment with microbubbles andultrasound. Furthermore, a hemorrhagic condition is often worsened bythe application of tPA. Ischemic stroke caused by a stenosis such as ablood clot is the type of stroke that an embodiment of the presentinvention is designed to treat. Accordingly it is desirable to initiallydetermine whether the stroke condition is hemorrhagic or ischemic. Oneway this may be done is by looking for a blood pool outside thevasculature, which is indicative of a hemorrhagic condition. A bloodpool will appear black in the standard ultrasound image since blood isnot a strong reflector of ultrasonic waves. The blood pool may alsoexhibit a lower rate of flow (Doppler velocity) than the flow of bloodin a containing blood vessel. After the contrast agent is introduced,the perfusion of the contrast agent into the microvasculature ofsurrounding tissue can create a slight halo effect of brighter contrastabout the darkened blood pool in an ultrasound image. It ischaracteristics such as these which can be used to identify whether thestroke is hemorrhagic or ischemic in origin.

In the depiction of FIG. 4, each image field 102, 104 is seen to extendalmost halfway across the cranium, which is a balance between the sizeof the image field and the acoustic penetration and attenuation whichmay be expected through the bone at the acoustic window. For somepatients, low attenuation effects may enable an image field to extendfully across the cranium, allowing the clinician to examine the vascularstructure near the skull bone on the opposite side of the cranium. Byalternately examining image fields of both transducer arrays, thevasculature across the full cranium may be effectively examined. It ispossible to acquire extended image fields which cover the same centralregion of the cranium but image from opposite sides of the head. Theseimages can be correlated and compounded together, forming a fused imagethat may reveal additional characteristics of the brain. The therapeuticbeam can also be transmitted from both sides of the head, enablingbreakup of a clot at both sides of the clot. Rather than be limited toreflective ultrasound imaging, through-transmission imaging can beperformed by transmitting ultrasound from one transducer array andreceiving the remaining unabsorbed ultrasonic energy at the othertransducer array, which may reveal yet other characteristics of thebrain tissue.

FIG. 5 illustrates a two dimensional imaging example of the presentinvention. In this example the transducer array 122 is a one dimensionalarray which performed 2D imaging. The array is configured as a circularphased array transducer as described in U.S. Pat. No. 5,226,422. Thistransducer array, like the other arrays described herein, is coveredwith a lens 124 which electrically insulates the patient from thetransducer array and in the case of a one dimensional array may alsoprovide focusing in the elevation (out-of-plane) dimension. Thetransducer array 122 is backed with acoustic damping material 126 whichattenuates acoustic waves emanating from the back of the array toprevent their reflection back into the transducer elements. Behind thistransducer stack is a device 130 for rotating the image plane 140 of thearray. The device 130 may be a simple knob or tab which may be graspedby the clinician to manually rotate the circular array transducer in itsrotatable transducer mount (not shown). The device 130 may also be amotor which is energized through a conductor 132 to mechanically rotatethe transducer as discussed in U.S. Pat. No. 5,181,514 (Solomon et al.)Rotating the one dimensional array transducer 122 as indicated by arrow144 will cause its image plane 140 to pivot around its central axis,enabling the repositioning of the image plane for full examination ofthe vasculature in front of the transducer array. As discussed in the'514 patent, the planes acquired during at least a 180° rotation of thearray will occupy a conical volume in front of the transducer array,which may be rendered into a 3D image of that volumetric region. Otherplanes outside this volumetric region may be imaged by repositioning,rocking or tilting the transducer array in its headset in relation tothe skull 100. If a stenosis is found in the image of the plane beingimaged, the therapeutic beam vector graphic 142 can be steered by theclinician to aim the beam at the stenosis and therapeutic pulses appliedto disrupt the microbubbles at the site of the stenosis.

It is common in the case of stroke that the affliction will not manifestitself in a single episode, but in repeated episodes as a blood clot orobstruction in the heart, lungs, or blood vessel breaks up gradually,releasing small clots which successively make their way to the vascularsystem of the brain over time. Thus, a patient who survives an initialstroke event, may be at risk for other events in the near future.Accordingly, it is desirable to monitor these patients for some timeafter an initial stroke event so that recurrences can be treatedimmediately. In accordance with a further aspect of the presentinvention, an embodiment of the invention may be used for the monitoringof stroke victims for recurrent events. The transducer arrays 10 a,10 b,microbeamformers 12 a,12 b, and multiplexer 14 can be efficientlypackaged in a flip-chip configuration as part of the headset. Thesecomponents can be battery powered and the output of the multiplexerconnected to an r.f transmitter. A fixed image field 102,104 iscontinually imaged as shown in FIG. 4; it is not necessary to be able tosteer or reposition the image field in this embodiment. The image dataproduced by the microbeamformers 12 a,12 b is wirelessly transmitted toa base unit as described in U.S. Pat. No. 6,113,547 (Catallo et al.) Atthe base station additional beamforming can be performed if necessary aswell as the image processing and display functions of the system ofFIG. 1. If a patient is not ambulatory a wireless connection may not benecessary and a wired connection to the base station may be employed.The wireless connection is also useful when the headset is being appliedby individuals having minimal experience with the device. For example, afirst responder may be unsure that the headset is applied properly andis acquiring a satisfactory image data set of the patient's vasculature.In that case the images can be transmitted to a base station, hospitalor other location where experienced personnel can view the images inreal time and talk the first responder through a successful applicationof the headset on the patient.

In the present example, image display is not necessary for themonitoring application. As successive images of the vasculature areformed at the base station they are stored in an image store 52, andtemporally different images are compared to detect changes in flow ofthe vasculature by operation of flow change detector 50. The flow changedetector operates by comparing the identical nature of the temporallydifferent images, similar to the image data correlation techniques usedto identify motion by image processing as described in U.S. Pat. No.6,442,289 (Olsson et al.) As long as successive images and imagesseparated by greater time intervals appear substantially the same intheir flow characteristics, e.g., there is no localized change in theflow characteristics of a particular section of the vasculature and nosection of the vasculature has ceased to return a Doppler signalindicating the continuation of flow, the flow change detector 50 willcontinue its monitoring of the vasculature with no change. For example,the vasculature may appear as the vascular network 300 of FIG. 6a for anextended period, and suddenly a section of the flow may cease to bedetected as illustrated by the absence of vessels 302 in FIG. 6c . If aflow change such as one of those indicated above is detected by the flowchange detector 50, an alarm is activated such as an audible alarm 42 ata nurse's station. Medical assistance can then be brought immediately tothe patient. In addition, the images stored in the image store at thetime of the detected flow change can be examined by medical personnel todiscern exactly where in the vasculature the detected obstructionoccurred. Therapy can then be directed specifically to the site of theobstruction without the need to closely examine a series of vascularmaps.

Since this is a monitoring application, image acquisition does not haveto be performed at the high rates necessary for real time imaging. A newimage could be acquired every second, for example, or at greaterintervals between image acquisitions. The lower acquisition rate ishelpful for conserving battery power in an ambulatory implementationwith an r.f. link. The lower image rate also permits images frommultiple patients to be processed in a time-interleaved manner by thesame system, which is useful for a nurse's station which needs tomonitor multiple patients.

During long term monitoring or monitoring of ambulatory patients it ispossible that the headset may move relative to the head of the patient,causing a difference between successive images from a transducer 10 a,10 b which has moved. Such movement can also cause a specific anatomicalregion being monitored to move outside of the image field of thetransducer array 10 a or 10 b. While the flow change detector 50 can bedesigned to be immune to such global changes and look only for localizedchanges in flow, it may be desirable to alert medical personnel toreadjust the headset or to reacquire target anatomy in the image field.This is done in the embodiment of FIG. 1 by means of an image fieldcontroller 54, which performs image analysis of temporally differentimages to detect changes in global alignment of the image data. If theheadset has not moved between successive images, for example, thesuccessive images of each transducer array will be the same and theimage data of the images will exhibit a high degree of correlation. Theimage analysis techniques used to measure image alignment in U.S. Pat.No. 5,556,674 (Weng), U.S. Pat. No. 6,572,549 (Jong et al.) or U.S. Pat.No. 6,589,176 (Jago et al.) and others may be used to perform the imagecomparison, for instance. Movement of the headset will result in aglobal change in correlation, which can alert medical personnel toadjust the headset. A local change in correlation may be a localizedflow change that should be detected by the flow change detector 50 orthe local decorrelation can be used to alert medical personnel to checkthe patient's condition. Another possibility is to use the globalcorrelation vector as an indication of image-to-image motion. Themotional change is then used by the transmit controller 18 to adjust thesteering of beams of the image field 102, 104, 140 to relocate theanatomy in the same position in the newly acquired image field, as inthe manner of image stabilization discussed in the aforementioned U.S.Pat. No. 6,589,176. This will enable the anatomy initially monitored bythe system to remain in view and in the image data set despite smallchanges in the headset positioning. If the target anatomy moves beyondthe range of beam steering reacquisition, an alert can be issued formedical personnel to reposition the headset. Such resteering correctionin the presence of motion can similarly be used to keep the therapeuticpencil beam 110, 112 constantly directed at a targeted blood clot beingtreated.

A typical sequence for a monitoring implementation of the presentinvention is illustrated by the flowchart of FIG. 7. The headset withthe array transducers is put on the patient at step 60 and images areinitially displayed and reviewed until the headset is adjusted so thatflow is observed in the images in step 62. When it is determined thatimages of cranial flow are being acquired, image display is no longernecessary and the headset is tightened in place on the patient at step64. Periodically image data is acquired from the image field of thearrays and transmitted to the monitoring unit at step 80. At themonitoring unit the image data may be further processed as desired atstep 82, then the new image is compared to one or more previouslyacquired images at step 84. If the flow characteristics of the imagesare unchanged, periodic transmission, reception, and comparison of imagedata continues. But if the new image is different in a predeterminedflow characteristic, the flow change is detected at 86 and an alertissued at 88 for medical attention.

While the monitoring implementation can be performed with 2D (planar)imaging, it is preferred that 3D imaging be used so that a largervolumetric region can be monitored. Monitoring can be performed withonly one transducer array, but a greater number of arrays likewiseprovides monitoring of a larger region of the cranium.

What is claimed is:
 1. A stroke therapy system for treating cranialvascular obstructions comprising: a transducer array headset adapted tomaintain an ultrasonic transducer array in acoustic contact with a headof a subject; a two dimensional array of transducer elements, located inthe headset, the elements configured to steer both imaging beams andtherapeutic beams over a volumetric region in the head of the subject; amicrobeamformer, located in the headset and coupled to the elements ofthe two dimensional array of transducer elements; a transmit controller,coupled to the array of transducer elements, and configured to cause theelements to transmit beams in either an imaging mode or a therapy mode;an image processor, coupled to the microbeamformer, which is configuredto produce harmonic images of microbubbles in the blood flow in thecranium of the subject when the elements are steering imaging beams overan imaged region of the cranium in the imaging mode; an image display,coupled to the image processor, which is configured to produce an imageof the cranial vasculature; and a user control which is adapted to bemanipulated by a user to aim a therapeutic beam vector on the imagedisplay at a location of an obstruction site in the image of the cranialvasculature, wherein the elements are caused to transmit a therapeuticbeam of a duty cycle of 50% or less which is aimed along the therapeuticbeam vector and focused at the obstruction site in the cranium of thesubject to vibrate or break the microbubbles at the obstruction sitewhen operated in the therapy mode.
 2. The stroke therapy system of claim1, wherein the image processor comprises a Doppler processor, whereinthe Doppler processor is configured to produce at least one of colorflowDoppler images or power Doppler images.
 3. The stroke therapy system ofclaim 1, wherein the two dimensional array of transducer elements isfurther configured to operate in the therapy mode to direct atherapeutic beam at the obstruction site in the cranium of the subject,wherein the therapeutic beam comprises an ultrasonic beam which iscapable of disrupting microbubbles at the obstruction site.
 4. Thestroke therapy system of claim 1, wherein the transducer array headsetis adapted to maintain the two dimensional array of transducer elementsin acoustic contact with one side of the head; and further comprising asecond two dimensional array of transducer elements located in theheadset and adapted to be maintained in acoustic contact with the otherside of the head by the headset.
 5. The stroke therapy system of claim4, wherein the first-named two dimensional array is configured to scanimaging beams over a majority of a cranial distance between the leftside of the head and the center of the cranium; and wherein the secondtwo dimensional array is configured to scan imaging beams over amajority of a cranial distance between the right side of the head andthe center of the cranium.
 6. The stroke therapy system of claim 1,wherein the transmit controller further is configured to cause the twodimensional array of transducer elements to transmit beams in theimaging mode for at least one of Doppler or B mode imaging.
 7. Thestroke therapy system of claim 6, wherein the transmit controllerfurther is configured to cause the transducer array to transmit beamsfor imaging over an image field exhibiting a given lateral dimension inthe cranium, wherein the therapeutic beam exhibits a lateral dimensionwhich is less than the given lateral dimension.
 8. The stroke therapysystem of claim 6, wherein the transmit controller further is configuredto transmit image beams over an image field occupying a given spatialregion in the cranium, wherein the therapeutic beam is transmitted overa portion of the given spatial region.
 9. The stroke therapy system ofclaim 8, wherein the given spatial region is a volumetric region.
 10. Astroke therapy system for treating cranial vascular obstructionscomprising: a transducer array headset adapted to maintain an ultrasonictransducer array in acoustic contact with a head of a subject; a onedimensional array of transducer elements, located in the headset, andconfigured to steer both imaging beams and therapy beams over a planarregion in the head of the subject; a device coupled to the array oftransducer elements and configured for physically changing the planarregion in the head which is imaged by the one dimensional array oftransducer elements without disturbing the maintenance of acousticcoupling by the headset; an image processor, coupled to the onedimensional array of transducer elements, which is configured to produceharmonic images of microbubbles in the blood flow in an image plane inthe cranium of the subject; an image display, coupled to the imageprocessor, which is configured to produce an image of the cranialvasculature and the microbubbles; a user control which is adapted to bemanipulated by a user to align a displayed therapy beam vector at alocation of an obstruction site in the image; and a transmitter, coupledto the one dimensional transducer array, which is configured to causethe array of transducer elements to steer, focus, and transmit atherapeutic beam along the therapy beam vector at an energy whichvibrates, oscillates, or ruptures the microbubbles at the obstructionsite in the plane of the image, wherein imaging and delivery of thetherapeutic beam are done by a common one dimensional transducer array.11. The stroke therapy system of claim 1, wherein imaging and thetransmission of the therapeutic beam are both configured to be donewithin the limits for diagnostic ultrasound energy delivery to thesubject.
 12. The stroke therapy system of claim 10, wherein thetransmitter is configured to apply at least one of pulse width modulatedor duty cycle modulated signals to the transducer array.
 13. The stroketherapy system of claim 10, wherein the one dimensional array is adaptedto be maintained in acoustic contact with one side of the head; furthercomprising a second one dimensional array which is adapted to bemaintained in acoustic contact by the headset with the other side of thehead.
 14. A method for treating stroke comprising: applying a headsetcontaining first and second two dimensional arrays of transducerelements to the head of a subject with the transducer arrays in acousticcontact with opposite sides of the head; producing a harmonic ultrasoundimage of cranial flow from signals received from at least one of thetransducer arrays; securing the headset to maintain the transducerarrays in acoustic contact with the head; infusing the blood stream ofthe subject with microbubbles; producing an ultrasound image of cranialflow containing microbubbles; identifying the location of a stenosis inthe ultrasound image; manipulating a user control to align a therapybeam vector at the identified location of the stenosis in the image; andtransmitting a therapeutic ultrasound beam from one of the transducerarrays in the direction of the therapy beam vector and focused at thelocation of microbubbles imaged by the transducer array at the locationof the stenosis and at an energy which vibrates or destroys themicrobubbles at the location of the stenosis.
 15. The method of claim14, further comprising: detecting a stenosis in the ultrasound image ofcranial flow containing microbubbles; and directing a therapeuticultrasound beam from at least one of the transducer arrays tomicrobubbles proximal to the stenosis.
 16. The method of claim 15wherein directing the therapeutic ultrasound beam further comprisessteering a pencil beam to microbubbles proximal to the stenosis.
 17. Themethod of claim 15 wherein directing the therapeutic ultrasound beamfurther comprises vibrating microbubbles proximal to the stenosis. 18.The method of claim 15 wherein directing the therapeutic ultrasound beamfurther comprises breaking microbubbles proximal to the stenosis. 19.The method of claim 15, wherein directing the therapeutic ultrasoundbeam further comprises transmitting the therapeutic ultrasound beam tomicrobubbles proximal to the stenosis at an energy level which is withinthe limits for diagnostic ultrasound.
 20. The method of claim 14,wherein producing an ultrasound image further comprises producing athree dimensional ultrasound image.